The capability to carry out multiple reactions in one flask is an important goal in chemistry because of the need to speed the synthesis of molecules while producing less waste and requiring fewer hours of effort. These reactions are often called cascade or domino reactions; their names refer to how several reactions occur in a predicted sequence in the same reaction vessel. These reactions are examples of green chemistry because they require less solvent and produce less waste than the traditional method of isolating and characterizing products after each reaction. Numerous cascade reactions have been developed, and many of them use one catalyst that catalyzes multiple steps.
The use of single catalysts to carry out multiple reactions has been very successful, but these cascade reactions typically require the development of new catalysts and cannot be integrated with numerous homogeneous catalysts that are commercially available and are excellent catalysts for one reaction. The main reason for this limitation is that these catalysts often poison one another or are poisoned by reagents required by a second catalyst. Thus, only one can be added to a reaction vessel, and no cascade sequence is possible. What is needed to advance the field of cascade reactions is a new method to integrate multiple catalysts and reagents.
Because many catalysts and reagents poison one another, they must be site-isolated from each other, such that multiple catalysts or reagents can be integrated into one reaction vessel for cascade reactions. Site-isolation involves modifying the catalysts or reagents such that they do not come into contact and poison one another. Numerous methods for site-isolation exist, such as attachment to a polymer backbone, attachment of a catalyst to a solid polymeric support, attachment of catalysts to a heterogeneous surface, trapping a catalyst inside a zeolite cage, or using catalytic enzymes in which the active sites are protected by the enzyme from interacting with the active site of another enzyme. These methods have been very successful in some instances: for example, Frechet and Hawker attached both acidic and basic residues to the interiors of star polymers to integrate acid- and base-catalyzed reactions in one vessel. In another example, heterogeneous acidic and basic clays were added to the same reaction vessel to carry out concurrent acid- and base-catalyzed reactions.
One critical limitation that hinders current cascade reaction development is that most methods for site-isolation require the structure of the catalyst be altered for attachment to a polymer or solid support. These alterations may require several synthetic steps and affect the reactivity and selectivity of catalysts, or may simply not be possible with a wide variety of reagents.